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Adrenergic activation confers cardioprotection mediated by adenosine, but is not required for ischemic
R Haessler1, K Kuzume, R A Wolff
1Department of Anesthesiology, Oregon Health Sciences University, Portland, USA.
Insights
Adrenergic activation protects the heart via adenosine receptors. However, ischemic preconditioning, a heart-protective mechanism, does not require alpha-adrenergic activation, despite also involving adenosine.
Area of Science:
- Cardiovascular Physiology
- Pharmacology
- Cellular Biology
Background:
- Investigating the role of adrenergic activation in cardioprotection.
- Examining the involvement of adenosine receptors in adrenergic cardioprotection.
- Determining the necessity of alpha-adrenergic activation for ischemic preconditioning.
Purpose of the Study:
- To ascertain if adrenergic activation confers cardioprotection.
- To determine if adenosine receptor activation mediates adrenergic cardioprotection.
- To assess if alpha-adrenergic activation is essential for ischemic preconditioning.
Main Methods:
- Open chest rabbits subjected to coronary occlusion and reperfusion.
- Ischemic preconditioning induced via brief coronary occlusion and reperfusion.
- Pharmacological agents used: tyramine for adrenergic activation, 8-p-sulfophenyl theophylline for adenosine receptor blockade, prazosin for alpha-1 adrenergic blockade, and phentolamine for non-selective alpha-adrenergic blockade.
Main Results:
- Ischemic preconditioning significantly reduced infarct volume by 79%.
- Adenosine receptor blockade attenuated the protective effects of both ischemic preconditioning and tyramine-induced adrenergic activation.
- Tyramine administration increased norepinephrine levels and reduced infarct volume by 55%, a protection abolished by adenosine receptor blockade.
- Blockade of alpha-1 or non-selective alpha-adrenergic receptors did not abolish the cardioprotection afforded by ischemic preconditioning.
Conclusions:
- Both ischemic preconditioning and alpha-adrenergic activation-induced cardioprotection involve adenosine.
- Ischemic preconditioning does not necessitate alpha-adrenergic activation for its cardioprotective effects.
Background:
The aim of this study was to determine whether (1) adrenergic activation is cardioprotective, (2) adrenergic cardioprotection occurs via adenosine receptor activation, and (3) ischemic preconditioning requires alpha-adrenergic activation.
Methods:
Anesthetised open chest rabbits underwent 30 min coronary occlusion and 3 h reperfusion. Ischemic preconditioning was elicited with 5 min coronary occlusion and 10 min reperfusion. Activation of adrenergic receptors with endogenous norepinephrine was achieved with tyramine (0.28 mg/kg/min intravenously for 5 min). Adenosine receptors were blocked with 8-p-sulfophenyl theophylline (10 mg/kg intravenously), alpha 1-adrenergic receptors were selectively blocked with prazosin (0.1 mg/kg intravenously), and alpha-adrenergic receptors were blocked with phentolamine (4 mg/kg intravenously).
Results:
Ischemic preconditioning reduced risk-adjusted infarct volume by 79% (P < 0.0005). This protection was attenuated by adenosine receptor blockade. Tyramine infusion resulted in a 1305% change from baseline plasma norepinephrine concentration (P < or = 0.01), and reduced infarct volume by 55% (P = 0.01). Adenosine receptor blockade abolished this protection. Blockade of alpha 1-adrenergic receptors with prazosin failed to abolish ischemic preconditioning (79 versus 89% reduction in infarct volume, without and with prazosin, respectively). Similarly, non-selective blockade of alpha-adrenergic receptors also failed to abolish ischemic preconditioning (79 versus 57% reduction without and with phentolamine, respectively).
Conclusions:
We conclude that the cardioprotection of ischemic preconditioning and alpha-adrenergic activation both involve adenosine, but ischemic preconditioning does not require alpha-adrenergic activation.